Aging in the female reproductive system of the rat is characterized by altered patterns of phasic LH secretion, leading to anovulatory estrous cycles. Changes in the preovulatory LH surge may represent loss of temporal organization following functional changes in the suprachiasmatic nuclei (SCN) which control most, if not all, circadian rhythms in rats. Since SCN is rich in serotonin (5-HT), a putative neurotransmitter implicated in control of the LH surge, altered daily patterns of 5-HT metabolism in SCN of aging rats may lead to reproductive senescence. Dynamics of 5-HT metabolism will be determined in SCN punched from hypothalamic tissue of rats killed at various times throughout a 24-hour period. Five-HT content and turnover after pargyline treatment will be determined by microradioenzymatic assay; 3H-5-HT synthesized from 3H-tryptophan will be isolated by ion-exchange chromatography. Daily metabolic profiles for SCN:5-HT in adult female rats showing regular estrous cycles will be compared with those from rats at different stages of their reproductive life spans including puberty, early sequence (period or irregular estrous cycles) and late senescence (constant estrus). Phase relationships of the SCN:5-HT and serum LH circadian rhythms and the light:dark cycle will be determined. Daily changes in LH secretion will be evaluated after local SCN microinjection of 5,7-dihydroxytryptamine, a 5-HT cell neurotoxin, to determine if serotonergic axon terminals in SCN are required for phasic secretion of LH. Exposure to constant light or induced, mild hyperthyroidism, which both cause estrous-cycle irregularity followed by constant estrus, will be used to determine how SCN:5-HT rhythms change during and after loss of reproductive cyclicity. Conversely, daily patterns of SCN:5-HT metabolism will be evaluated in old, previously acyclic rats in which estrous cycles are restored by reduced light exposure or by stress, and in chronically underfed rats whose reproductive-life span is prolonged by caloric restriction. SCN:5-HT rhythms will be established in constant-estrous rats by microinjection of the amine or its agonist (quipazine) in an attempt to reinstate phasic LH secretion. These experiments will test the hypothesis that age-related neurochemical change in SCN promote reproductive senescence in female rats.